rs17202296

Variant names:

• chr16-81925586-G-C
• rs17202296
• NM_002661.5:c.2418-1496G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002661.5(PLCG2):​c.2418-1496G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,150 control chromosomes in the GnomAD database, including 4,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4584 hom., cov: 32)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 4 publications found

Genes affected

PLCG2 (HGNC:9066): (phospholipase C gamma 2) The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]

PLCG2 Gene-Disease associations (from GenCC):

• autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial cold autoinflammatory syndrome 3

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.2418-1496G>C		intron_variant	Intron 22 of 32	ENST00000564138.6	NP_002652.2
PLCG2	NM_001425749.1	c.2418-1496G>C		intron_variant	Intron 23 of 33		NP_001412678.1
PLCG2	NM_001425750.1	c.2418-1496G>C		intron_variant	Intron 22 of 32		NP_001412679.1
PLCG2	NM_001425751.1	c.2418-1496G>C		intron_variant	Intron 23 of 33		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.2418-1496G>C		intron_variant	Intron 22 of 32	1	NM_002661.5	ENSP00000482457.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37058 AN: 152032 Hom.: 4582 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37077 AN: 152150 Hom.: 4584 Cov.: 32 AF XY: 0.241 AC XY: 17896 AN XY: 74394

African (AFR) AF: 0.228 AC: 9472 AN: 41498

American (AMR) AF: 0.199 AC: 3047 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3468

East Asian (EAS) AF: 0.185 AC: 956 AN: 5180

South Asian (SAS) AF: 0.310 AC: 1497 AN: 4822

European-Finnish (FIN) AF: 0.244 AC: 2586 AN: 10596

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17733 AN: 67992

Other (OTH) AF: 0.247 AC: 521 AN: 2112

Alfa AF: 0.101 Hom.: 171

Bravo AF: 0.236

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17202296; hg19: chr16-81959191;